oxytocin and Anxiety--Separation

The hormone oxytocin plays an important role in attachment formation and bonding between humans and domestic dogs. Recent research has led to increased interest in potential applications for intranasal oxytocin to aid with the treatment of psychological disorders in humans. While a few studies have explored the effects of intranasally administered oxytocin on social cognition and social bonding in dogs, alternative applications have not yet been explored for the treatment of behavioural problems in this species. One potentially important application for intranasal oxytocin in dogs could be the treatment of separation anxiety, a common attachment disorder in dogs. Here we provide an overview of what is known about the role of oxytocin in the human-dog bond and canine separation anxiety, and discuss considerations for future research looking to integrate oxytocin into behavioural treatment based on recent findings from both the human and dog literature.

Topics: Animals; Anxiety, Separation; Dogs; Human-Animal Bond; Humans; Oxytocin

Topics: Animals; Anxiety, Separation; Cathexis; Dopamine; gamma-Aminobutyric Acid; Gene Expression Regulation; Genes, fos; Humans; Limbic System; Mammals; Mental Disorders; Models, Biological; Morphine; Opioid Peptides; Oxytocin; Rats; Receptors, Opioid, mu; Stress, Physiological; Substance-Related Disorders; Tegmentum Mesencephali

Adaptations to stress can occur through epigenetic processes and may be a conduit for informing offspring of environmental challenge. We employed ChIP-sequencing for H3K4me3 to examine effects of early maternal deprivation (peer-rearing, PR) in archived rhesus macaque hippocampal samples (male,

Topics: Adaptation, Psychological; Alleles; Animals; Anxiety, Separation; Epigenesis, Genetic; Female; Hippocampus; Histones; Macaca mulatta; Male; Maternal Deprivation; Oxytocin; Polymorphism, Single Nucleotide; Receptors, Oxytocin; Stress, Physiological

Anxiety disorders are common in youth and cause significant distress and impairment to the individual and family. Oxytocin (OT), a nine amino acid peptide, is implicated in anxiety regulation and modulation of close interpersonal and attachment behavior. Anxiety disorders have been linked to low levels of salivary OT in youth. Research has also linked oxytocinergic functioning to social support, warm contact, and bonding, and indicated that contact with attachment figures stimulates OT response. We examined OT response to a brief, positive youth-mother interaction in clinically anxious youth. We investigated whether quality of the youth-mother interaction as well as the presence of particular anxiety disorders, are associated with youth OT response.. Salivary OT from 41 youth with primary DSM-5 anxiety disorders was assayed before and after a 7-min youth-mother interaction that was later systematically coded by two reliable coders. Youth and mothers also completed rating scales of youth anxiety symptoms.. Affective touch, maternal sensitivity, maternal intrusiveness, youth engagement, and youth initiative all contributed significantly to predicting youth OT response. Repeated measures analyses showed that when affective touch was high youth had greater OT response. OT response was positively associated with the presence of separation anxiety disorder (SAD) and with child ratings of separation anxiety.. The findings highlight the importance of maternal and dyadic behavior patterns to oxytocinergic response in clinically anxious youth, shed light on the association between OT and SAD, and point to possible intervention strategies.

Topics: Adolescent; Adolescent Behavior; Adult; Anxiety Disorders; Anxiety, Separation; Child; Child Behavior; Female; Humans; Male; Maternal Behavior; Middle Aged; Mother-Child Relations; Object Attachment; Oxytocin; Saliva

Clinical anxiety disorders in youth are common and associated with interpersonal behaviors including reliance on parents for family accommodation, or changes that parents make to their own behaviors to help the youth avoid anxiety related distress. The neuropeptide oxytocin is associated with the regulation of anxiety and of close interpersonal behavior leading to the hypothesis that oxytocinergic functioning plays a role in youth anxiety and its disorders, and the resulting family accommodation. To test this hypothesis salivary OT from 50 youth with primary DSM-5 anxiety disorders was assayed. A multi-source/multi-method anxiety assessment including semistructured interviews with youth and mothers, rating scales, and behavioral observations was used to assess anxiety disorders and symptoms, and family accommodation. Youth with separation anxiety disorder had significantly lower salivary OT levels than clinically anxious youth not diagnosed with separation anxiety disorder. Salivary OT levels were significantly negatively correlated with separation anxiety symptoms based on both youth- and mother-ratings. Anxious behavior displayed by youth during interactions with their mothers was associated with lower salivary OT levels in youth. Maternal ratings of family accommodation were negatively associated with salivary OT levels in youth. Results support the role of the oxytocinergic system in youth anxiety and its disorders and in parental involvement in youth anxiety through family accommodation. OT may be particularly important for diagnoses and symptoms of separation anxiety, which is inherently interpersonal in nature. Findings have potentially important implications for assessment and treatment of anxiety in youth.

Topics: Adolescent; Anxiety, Separation; Child; Female; Humans; Male; Mother-Child Relations; Mothers; Oxytocin; Pituitary Hormones; Saliva; Self Report; Surveys and Questionnaires

Consolation behavior toward distressed others is common in humans and great apes, yet our ability to explore the biological mechanisms underlying this behavior is limited by its apparent absence in laboratory animals. Here, we provide empirical evidence that a rodent species, the highly social and monogamous prairie vole (Microtus ochrogaster), greatly increases partner-directed grooming toward familiar conspecifics (but not strangers) that have experienced an unobserved stressor, providing social buffering. Prairie voles also match the fear response, anxiety-related behaviors, and corticosterone increase of the stressed cagemate, suggesting an empathy mechanism. Exposure to the stressed cagemate increases activity in the anterior cingulate cortex, and oxytocin receptor antagonist infused into this region abolishes the partner-directed response, showing conserved neural mechanisms between prairie vole and human.

Topics: Animals; Anxiety; Anxiety, Separation; Arvicolinae; Corticosterone; Emotions; Female; Helping Behavior; Injections, Intraventricular; Male; Oxytocin; Stress, Psychological

Clinically significant separation anxiety [SA] has been identified as being common among patients who do not respond to psychiatric interventions, regardless of intervention type (pharmacological or psychotherapeutic), across anxiety and mood disorders. An attachment formation and maintenance domain has been proposed as contributing to anxiety disorders. We therefore directly determined prevalence of SA in a population of adult treatment non-responders suffering from primary anxiety. In these separation anxious nonresponders, we pilot-tested an SA-focused, attachment-based psychotherapy for anxiety, Panic-Focused Psychodynamic Psychotherapy-eXtended Range [PFPP-XR], and assessed whether hypothesized biomarkers of attachment were engaged. We studied separation anxiety [SA] in 46 adults (ages 23-70 [mean 43.9 (14.9)]) with clinically significant anxiety symptoms (Hamilton Anxiety Rating Scale [HARS]≥15), and reporting a history of past non-response to psychotherapy and/or medication treatments. Thirty-seven (80%) had clinically significant symptoms of separation anxiety (Structured Clinical Interview for Separation Anxiety Symptoms [SCI-SAS] score≥8). Five of these subjects completed an open clinical trial of Panic Focused Psychodynamic Psychotherapy eXtended Range [PFPP-XR], a 21-24 session, 12-week manualized attachment-focused anxiolytic psychodynamic psychotherapy for anxiety. Patients improved on "adult threshold" SCI-SAS (current separation anxiety) (p=.016), HARS (p=0.002), and global severity, assessed by the Clinical Global Impression Scale (p=.0006), at treatment termination. Salivary oxytocin levels decreased 67% after treatment (p=.12). There was no significant change in high or low frequency HRV after treatment, but change in high frequency HRV inversely correlated with treatment change in oxytocin (p<.02), and change in low frequency HRV was positively associated with change in oxytocin (p<.02). SA is surprisingly prevalent among non-responders to standard anti-anxiety treatments, and it may represent a novel transdiagnostic target for treatment intervention in this population. Anxiety and global function improved in a small trial of a brief, manualized, attachment-focused psychodynamic psychotherapy, potentially supporting the clinical relevance of attachment dysfunction in this sample. The large decrease in oxytocin levels with treatment, although not statistically significant in this very small sample, suggests the need for further study of

Topics: Adolescent; Adult; Aged; Anxiety Disorders; Anxiety, Separation; Biomarkers; Female; Heart Rate; Humans; Male; Middle Aged; Neuropsychological Tests; Object Attachment; Oxytocin; Psychotherapy; Psychotherapy, Psychodynamic; Syndrome; Treatment Outcome; Young Adult

We interrogated the genetic modulation of maternal oxytocin response and its association with maternal behavior using genetic risk scores within the oxytocin receptor (OXTR) gene. We identified a novel SNP, rs968389, to be significantly associated with maternal oxytocin response after a challenging mother-infant interaction task (Still Face Paradigm) and maternal separation anxiety from the infant. Performing a multiallelic analysis across OXTR by calculating a cumulative genetic risk score revealed a significant gene-by-environment (G × E) interaction, with OXTR genetic risk score interacting with adult separation anxiety to modulate levels of maternal sensitivity. Mothers with higher OXTR genetic risk score and adult separation anxiety showed significantly reduced levels of maternal sensitivity during free play with the infant. The same G × E interaction was also observed for the extended OXTR cumulative genetic risk score that included rs968389. Moreover, the extended cumulative OXTR genetic risk score itself was found to be significantly associated with maternal separation anxiety as it specifically relates to the infant. Our results suggest a complex montage of individual and synergistic genetic mediators of maternal behavior. These findings add to specific knowledge about genetic regulation of maternal oxytocin response in relation to maternal adjustment and infant bonding through the first few months of life.

Topics: Adult; Anxiety, Separation; Cohort Studies; Female; Gene-Environment Interaction; Humans; Infant; Longitudinal Studies; Maternal Behavior; Oxytocin; Polymorphism, Single Nucleotide; Pregnancy; Receptors, Oxytocin; Single-Blind Method; Surveys and Questionnaires

In this paper, we aimed to assess cross-sectionally and longitudinally associations between disturbances in maternal early attachment experiences, symptoms of separation anxiety and depression and oxytocin plasma levels. We examined a mediational model that tested the hypothesis that anxious attachment style arising from the mothers' early bonding experiences with her own parents was associated with high levels of separation anxiety which, via its impact on depression, was associated with reduced levels of oxytocin in the postnatal period. Data is reported on a structured sample of 127 women recruited during pregnancy from a general hospital antenatal clinic and an initial follow up cohort of 57 women who were re-assessed at 3-months post-partum. We found an association between lower oxytocin level in the post partum period and symptoms of separation anxiety and depression during pregnancy, as well as maternal negative interpersonal representations, upbringing attributes and anxious attachment style. Further meditational analysis revealed that the unique association between anxious attachment and depression is mediated by separation anxiety and that depressed mood mediated the relationship between separation anxiety and oxytocin. In conjunction with evidence from the literature suggesting that lower oxytocin level is associated with bonding difficulties, our findings have significant implications for understanding the biological processes underpinning adverse attachment experiences, negative affect state, and mother-to-infant bonding difficulties.

Topics: Adolescent; Adult; Anxiety, Separation; Cross-Sectional Studies; Depression, Postpartum; Female; Humans; Infant; Longitudinal Studies; Middle Aged; Models, Psychological; Mother-Child Relations; Object Attachment; Oxytocin; Parents; Pregnancy; Young Adult

Exposure to early life stress causes increased stress responsiveness and permanent changes in the central nervous system. We recently showed that delayed gastric emptying (GE) and accelerated colonic transit (CT) in response to acute restraint stress (ARS) were completely restored following chronic homotypic stress (CHS) in rats via upregulation of hypothalamic oxytocin (OXT) expression. However, it is unknown whether early life stress affects hypothalamic OXT circuits and gastrointestinal motor function. Neonatal rats were subjected to maternal separation (MS) for 180 min/day for 2 wk. Anxiety-like behaviors were evaluated by the elevated-plus-maze test. GE and CT were measured under nonstressed (NS), ARS, and CHS conditions. Expression of corticotropin-releasing factor (CRF) and OXT in the paraventricular nucleus (PVN) of the hypothalamus was evaluated by real time RT-PCR and immunohistochemistry. MS increased anxiety-like behaviors. ARS delayed GE and accelerated CT in control and MS rats. After CHS, delayed GE and accelerated CT were restored in control, but not MS, rats. CRF mRNA expression was significantly increased in response to ARS in control and MS rats. Increased CRF mRNA expression was still observed following CHS in MS, but not control, rats. In response to CHS, OXT mRNA expression was significantly increased in control, but not MS, rats. The number of OXT-immunoreactive cells was increased following CHS in the magnocellular part of the PVN in control, but not MS, rats. MS impairs the adaptation response of gastrointestinal motility following CHS. The mechanism of the impaired adaptation involves downregulation of OXT and upregulation of CRF in the hypothalamus in MS rats.

Topics: Adaptation, Physiological; Animals; Animals, Newborn; Anxiety, Separation; Chronic Disease; Female; Gastrointestinal Motility; Gene Expression Regulation; Hypothalamus; Male; Oxytocin; Rats; Rats, Sprague-Dawley; Stress, Psychological

Individuals with a diagnosis of adult separation anxiety (ASAD) have extreme anxiety about separations, actual or imagined, from major attachment figures. ASAD might represent a psychological/behavioral model for research probably involving a dysregulation of those neurobiological mechanisms of attachment, in particular central oxytocin (OT), described in numerous animal studies. As experimental strategy, we chose the nucleotidic sequencing of the human OT gene of patients with ASAD to evaluate whether OT mutations were related to potential alteration of its production. With this aim, mutation scanning of proximal promoter and untranslated and coding regions of the OT gene was carried out in 36 patients with ASAD, 14 patients without ASAD, and 26 controls. No mutations were found in promoter and coding regions of the OT gene in our population. One rare 3'UTR single nucleotide variant (rs17339677) and one intron 2 molecular variant (rs34097556), which showed a high frequency, were evidenced. There was no significant difference in the genotype distribution of this intron 2 polymorphism between patients and healthy individuals. Further research is needed to investigate the association between ASAD and OT peptide and receptor polymorphisms.

Topics: 3' Untranslated Regions; Adult; Age Factors; Age of Onset; Anxiety, Separation; DNA Mutational Analysis; Female; Gene Frequency; Genetic Predisposition to Disease; Genetic Variation; Genotype; Humans; Introns; Male; Mutation; Oxytocics; Oxytocin; Polymorphism, Genetic; Polymorphism, Single Nucleotide; Promoter Regions, Genetic; Regulatory Sequences, Nucleic Acid

The development of brain oxytocin (OXT) receptors was examined following the mild stress of daily, 20 min separations of infant rats from their mothers (repeated separation condition) or in undisturbed controls. Changes in OXT receptors were characterized in cell membrane preparations, using the OXT receptor ligand [125I]d(CH2)5[Tyr(Me)2Thr4Tyr-NH9(2)]-ornithine vasotocin ([125I]OTA), from rats at 4, 8, 14, 22 postnatal days of age or as adults. In the hippocampus of control animals, [125I]OTA binding was highest at day 4 or 8 and declined thereafter. Repeated separation decreased the Bmax of [125I]OTA binding in whole hippocampus at day 8, an effect that did not persist into adulthood. This effect was found to be confined to the rapidly proliferating, dorsal hippocampus. It has been suggested that brain OXT is involved in both affiliative/social and stress-related behaviors. While the specific function of OXT receptors in hippocampus is currently unknown, mild stress to the infant and the disruption of infant-mother contact transiently alters the normal development of this system.

Topics: Animals; Animals, Newborn; Anxiety, Separation; Female; Hippocampus; Male; Oxytocin; Rats; Rats, Sprague-Dawley; Receptors, Oxytocin; Stress, Psychological; Vasotocin

Topics: Animal Communication; Animals; Anxiety, Separation; Chickens; Dose-Response Relationship, Drug; Feeding Behavior; Oxytocin; Social Behavior; Social Isolation; Time Factors; Vasotocin

Topics: Animals; Anxiety, Separation; Dominance-Subordination; Male; Oxytocin; Saimiri; Sexual Behavior, Animal

Acetylcholinesterase (AChE) activity, and concentrations of monoamines, monoamine metabolites and oxytocin (OT) were measured in the cerebrospinal fluid (CSF) of sheep during late pregnancy, labour, parturition, vaginocervical stimulation, lamb separation and suckling. Concentrations of AChE, 4-hydroxy-3 methoxyphenylethan-1,2-diol (MHPG) and OT were significantly elevated during labour and parturition. OT levels were also significantly raised in cycling ewes given vaginocervical stimulation. Separation of the ewes from their lambs (0.5-2 h) caused significant increases in AChE and MHPG, but not in OT. During suckling, following reunion of the ewes and lambs, concentrations of AChE and OT were significantly raised. The dopamine metabolites 3,4-dihydroxyphenylacetic acid and homovanillic acid were significantly lower in CSF during late pregnancy than during parturition and post-partum. Intravenous injections of OT which produced high circulating levels of this hormone in plasma produced significant, but very small, increases in concentrations of OT in the CSF. Our results show that in the sheep, labour, parturition, suckling and vaginocervical stimulation provoke a release of OT in the brain similar to that in the peripheral circulation. Changes in CSF levels of AChE and MHPG during labour, parturition and lamb separation, but not during vaginocervical stimulation, may be related to stress or hypertension.

Topics: Acetylcholinesterase; Animals; Animals, Suckling; Anxiety, Separation; Biogenic Amines; Blood-Brain Barrier; Cervix Uteri; Female; Labor, Obstetric; Oxytocin; Pregnancy; Radioimmunoassay; Sheep; Vagina